The mechanisms by which T-cell costimulatory molecules enhance the activation of nanve and/or memory T cells are under investigation. Preliminary results have demonstrated that both nanve CD4+ and CD8+ T cells actually acquire the costimulatory molecule B7-1 from antigen-presenting cells (APCs) after activation. This phenomenon was demonstrated using B7-1/B7-2 knockout mice; moreover, no B7-1 mRNA could be detected in T cells that had acquired B7-1. The amount of acquisition of B7-1 by T cells was shown to be directly related to both (a) the strength of signal 1 and (b) the amount of B7-1 on the APC. Preliminary studies also indicate that nanve T cells, following acquisition of B7-1 from APCs, are themselves capable of acting as APCs. Moreover, preliminary results indicate that memory T cells that have acquired B7-1 from APCs can undergo apoptosis in the presence of increased levels of signal 1. These findings thus indicate that both immunostimulatory and immune regulatory functions can occur as a result of B7-1 acquisition by different T- cell populations. Studies are also ongoing to examine the mechanism by which dendritic cells, which hyperexpress costimulatory molecules by via TRICOM vector infection, activate T cells in vivo.